Increased Platelet Adhesiveness in Patients with Venous Thromboembolic Disease

被引:0
作者
Martinez-Sanchez, Julia [1 ,2 ]
Torramade-Moix, Sergi [1 ]
Moreno-Castano, Ana Belen [1 ,2 ]
Llobet, Dolors [3 ,4 ,5 ]
Jerez-Dolz, Didac [1 ]
Sanchez, Pablo [6 ]
Carrasco, Marina [3 ,4 ]
Mojal, Sergi [4 ]
Moret, Carla [3 ,4 ]
Camacho, Mercedes [4 ,7 ,8 ]
Soria, Jose Manuel [4 ,5 ,8 ]
Palomo, Marta [9 ]
Martin-Fernandez, Laura [10 ,11 ]
Vidal, Francisco [7 ,10 ,11 ]
Escolar, Gines [1 ]
Diaz-Ricart, Maribel [1 ]
Souto, Juan Carlos [3 ,4 ,5 ]
机构
[1] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Ctr Diagnost Biomed CDB,Dept Pathol,Hemostasis &, Barcelona, Spain
[2] Barcelona Endothelium Team, Barcelona, Spain
[3] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona, Spain
[4] Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
[5] Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
[6] Spanish Natl Res Council, Inst Ciencies Mar, Dept Marine Biol & Oceanog, Barcelona, Spain
[7] Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Cardiovasc CIBERCV, Madrid, Spain
[8] IIB St Pau, Genom & complex Dis Unit, Barcelona, Spain
[9] Hosp Clin Barcelona, CDB, Hematol External Qual Assessment Lab, Barcelona, Spain
[10] Blood & Tissue Bank, Congenital Coagulopathies Lab, Barcelona, Spain
[11] Univ Autonoma Barcelona VHIR UAB, Vall dHebron Res Inst, Transfus Med, Barcelona, Spain
关键词
closure times; intraplatelet protein; platelet adhesiveness; platelet aggregation; venous thromboembolism; VON-WILLEBRAND-FACTOR; DEEP-VEIN THROMBOSIS; FACTOR-VIII; RISK; ACTIVATION; COLLAGEN; ASPIRIN; VOLUME; PHOSPHORYLATION; MICROPARTICLES;
D O I
10.1055/s-0044-1800798
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Association between global platelet function and the risk of venous thromboembolic disease (VTE) has been proposed, though the mechanisms do not involve increased platelet aggregation. However, platelet adhesiveness has not been systematically explored in VTE patients. Objectives To evaluate platelet adhesive functions in VTE patients. Methods Platelet adhesion was evaluated by using whole blood samples from VTE patients, selected based on short closure times on the PFA-100 (n = 54), and matched healthy individuals (n = 57) in: (i) the PFA-100, (ii) a cone plate analyzer (CPA), on a plastic surface, (iii) microfluidic devices, with two- and three-dimensional evaluation, and (iv) membrane glycoprotein analysis. Intraplatelet signaling was evaluated in isolated collagen type I (Col-I) activated platelets and platelets adhered on Col-I or von Willebrand factor (VWF) coated coverslips under flow. VWF antigen and ADAMTS-13 activity were measured in plasma samples. Results PFA-100 closure times remained significantly shorter in patients. The CPA test showed a significant increase in the platelet aggregates size when using blood from VTE patients. Platelet adhesion on Col-I revealed a higher area covered by platelets and increased aggregate volume when exposed to samples from VTE patients. Protein P-ZAP70/SYK72 showed a phosphorylation level significantly increased in patients' platelets. Plasma VWF was significantly elevated in VTE patients. Conclusions Platelets from VTE patients exhibit a proadhesive phenotype under flow conditions potentially related to the shortened occlusion times with the PFA-100. This enhanced adhesiveness may be explained by higher intraplatelet ZAP70/SYK72 phosphorylation and increased plasma VWF in patients. Therefore, primary hemostasis plays a significant role in the pathophysiology of VTE.
引用
收藏
页码:e329 / e339
页数:11
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